The technology described herein relates to rapid and precise temperature control of fluid droplets having use in a number of applications, including in chemical and biological applications where temperature affects a reaction such as a binding event or reaction step. A particularly relevant biological application is polymerase chain reaction (PCR) where repeated thermal cycling is required for amplification of nucleotide sequences.
Advances in nanotechnology have facilitated the advance of integrated devices for electrical sensing of various biological parameters. For example, nanoscale field effect transistors have been incorporated into sensor arrays for detection, nucleotide sequencing and amplification applications. U.S. Pat. Pub. No. 20080280776 and PCT Pub. Nos. WO2010037085, WO2011163058 and WO2012078340 (Bashir et al.). Other groups have examined various aspects of fluid droplet manipulation, such as U.S. Pat. Pub. No. 20100096266 and U.S. Pat. No. 8,137,917. Those technologies, however, suffer from the disadvantage that the fluid droplets are either of relatively high thermal mass, require another liquid phase to ensconce or encapsulate an interior liquid such as an oil layer encapsulating a water-based fluid or are directed to fluid droplets that are themselves suspended in a bulk fluid. This adversely impacts the ability of those systems to independently, precisely and rapidly thermally control the temperature profile spatially within the droplet and with time. The systems and devices presented herein address those limitations by heating droplets of extremely low volume to ensure the droplets have low thermal mass, surrounding the droplets by a gas, and heating in a manner so that evaporation is minimized to ensure that even for applications requiring large number of thermal cycles (e.g., PCR), the fluid droplet maintains bulk integrity.